The major goal of the research effort was to precisely locate the von Hippel-Lindau disease gene. Previous studies from our laboratory indicated that VHL is located in a 6-8 cM interval between RAF1 and D3Sl8. D3S601 is the closest marker we have identified to the VHL gene; it is located in a region immediately surrounding the VHL gene. We have isolated YAC clones for all markers close to the VHL locus and are in the process of cloning the region by YAC-based chromosome walking. Forty-three probes homozygously deleted in a small cell lung carcinoma line were identified. Human squamous cell carcinomas of the head and neck were shown to be characterized by a loss of alleles at loci on chromosome 3p.